Candace Savonen - CCDL for ALSF

This notebook sets up the MAF data files for comparison and does some first line analyses.

It is the first notebook in this series which addresses issue # 30 in OpenPBTA.

Usage

To run this from the command line, use:

Rscript -e "rmarkdown::render('analyses/mutect2-vs-strelka2/01-set-up.Rmd', 
                              clean = TRUE)"

This assumes you are in the top directory of the repository.

Set Up

# We need maftools - this will be added to the running Docker issue whenever it is up
if (!("maftools" %in% installed.packages())) {
  devtools::install_github("PoisonAlien/maftools")
}

Get magrittr pipe

`%>%` <- dplyr::`%>%`

Directories and files

Path to the symlinked data obtained via bash download-data.sh.

data_dir <- file.path("..", "..", "data")
scratch_dir <- file.path("..", "..", "scratch")

Create output directories in this analysis folder.

if (!dir.exists("results")) {
  dir.create("results")
}
if (!dir.exists("plots")) {
  dir.create("plots")
}

Read in the metadata information

Running maftools::read.maf takes a lot of computing power and time, so to avoid having to run this for both datasets everytime we want to re-run this notebook or the analyses in the other notebook, I’ve set this up to save the MAF objects as RDS files.

First let’s establish the file paths.

# File paths for the needed files for this analysis
  metadata_dir <- file.path(scratch_dir, "metadata_filtered_maf_samples.tsv")
strelka2_dir <- file.path(scratch_dir, "strelka2.RDS")
mutect2_dir <- file.path(scratch_dir, "mutect2.RDS")

Read in the Strelka2 and Mutect2 data

Will read in as an maftools object from an RDS file, unless maftools has not been run on them yet. Establish whether the files we need for this already exist before running it again.

If you trying to run the set up step in a Docker container, it will likely be out of memory killed, unless you have ~50GB you can allot to Docker.

Prep the metadata to be used as the clinicalData for maftools it it hasn’t been prepped yet.

# Get a vector of whether these exist
files_needed <- file.exists(metadata_dir, strelka2_dir, mutect2_dir)

if (all(files_needed)) {
  # Read the ready-to-go files if these files exist
  metadata <- metadata <- readr::read_tsv(metadata_dir)
  strelka2 <- readRDS(strelka2_dir)
  mutect2 <- readRDS(mutect2_dir)
} else { # If any of the needed files don't exist, rerun this process:
  # Only import the sample names
  strelka2_samples <- data.table::fread(file.path(
    data_dir,
    "pbta-snv-strelka2.vep.maf.gz"
  ),
  select = "Tumor_Sample_Barcode",
  skip = 1,
  data.table = FALSE
  )

  mutect2_samples <- data.table::fread(file.path(
    data_dir,
    "pbta-snv-mutect2.vep.maf.gz"
  ),
  select = "Tumor_Sample_Barcode",
  skip = 1,
  data.table = FALSE
  )

  # Isolate metadata to only the samples that are in the datasets
  metadata <- readr::read_tsv(data_dir, "pbta-histologies.tsv") %>%
    dplyr::filter(Kids_First_Biospecimen_ID %in% c(strelka2_samples, mutect2_samples)) %>%
    dplyr::distinct(Kids_First_Biospecimen_ID, .keep_all = TRUE) %>%
    dplyr::arrange() %>%
    readr::write_tsv(file.path(scratch_dir, "metadata_filtered_maf_samples.tsv"))

  # Read in original strelka file with maftools
  strelka <- maftools::read.maf(file.path(data_dir, "pbta-snv-strelka2.vep.maf.gz"),
    clinicalData = metadata
  )

  # Save to RDS so we don't have to run this again
  saveRDS(strelka, strelka2_dir)

  # Same for MuTect2
  mutect2 <- maftools::read.maf(file.path(data_dir, "pbta-snv-mutect2.vep.maf.gz"),
    clinicalData = metadata
  )
  saveRDS(mutect2, mutect2_dir)
}
Parsed with column specification:
cols(
  .default = col_character(),
  age_at_diagnosis = col_double(),
  molecular_subtype = col_logical()
)
See spec(...) for full column specifications.

Get summaries and write them to TSVs

Get gene summaries and write to TSV files.

strelka2_gene_sum <- maftools::getGeneSummary(strelka2) %>%
  readr::write_tsv(file.path(
    "results",
    "strelka2_gene_summary.tsv"
  ))

mutect2_gene_sum <- maftools::getGeneSummary(mutect2) %>%
  readr::write_tsv(file.path(
    "results",
    "mutect2_gene_summary.tsv"
  ))

Get sample summaries and write to TSV files.

strelka2_sample_sum <- maftools::getSampleSummary(strelka2) %>%
  readr::write_tsv(file.path(
    "results",
    "strelka2_sample_summary.tsv"
  ))

mutect2_sample_sum <- maftools::getSampleSummary(mutect2) %>%
  readr::write_tsv(file.path(
    "results",
    "mutect2_sample_summary.tsv"
  ))

Number of mutations per gene correlation

combined_gene <- mutect2_gene_sum %>%
  dplyr::full_join(strelka2_gene_sum, by = "Hugo_Symbol") %>%
  reshape2::melt(id = "Hugo_Symbol") %>%
  dplyr::mutate(dataset = as.character(grepl(".x$", variable))) %>%
  dplyr::mutate(dataset = dplyr::recode(dataset,
    `TRUE` = "mutect2",
    `FALSE` = "strelka2"
  )) %>%
  dplyr::mutate(variable = gsub(".x$|.y$", "", variable)) %>%
  tidyr::spread("dataset", "value")

Let’s get a correlation test on the genes overall.

cor.test(combined_gene$mutect2, combined_gene$strelka2, method = "spearman")
Cannot compute exact p-value with ties

    Spearman's rank correlation rho

data:  combined_gene$mutect2 and combined_gene$strelka2
S = 4.7233e+13, p-value < 2.2e-16
alternative hypothesis: true rho is not equal to 0
sample estimates:
      rho 
0.9568251 
cor.test(combined_gene$mutect2, combined_gene$strelka2, method = "pearson")

    Pearson's product-moment correlation

data:  combined_gene$mutect2 and combined_gene$strelka2
t = 567.61, df = 187234, p-value < 2.2e-16
alternative hypothesis: true correlation is not equal to 0
95 percent confidence interval:
 0.7935980 0.7969277
sample estimates:
      cor 
0.7952689 

Number of mutations per sample correlation.

combined_sample <- mutect2_sample_sum %>%
  dplyr::full_join(strelka2_sample_sum, by = "Tumor_Sample_Barcode") %>%
  reshape2::melt(id = "Tumor_Sample_Barcode") %>%
  dplyr::mutate(dataset = as.character(grepl(".x$", variable))) %>%
  dplyr::mutate(dataset = dplyr::recode(dataset,
    `TRUE` = "mutect2",
    `FALSE` = "strelka2"
  )) %>%
  dplyr::mutate(variable = gsub(".x$|.y$", "", variable)) %>%
  tidyr::spread("dataset", "value")

Let’s get a correlation test on the genes overall.

cor.test(combined_sample$mutect2, combined_sample$strelka2, method = "spearman")
Cannot compute exact p-value with ties

    Spearman's rank correlation rho

data:  combined_sample$mutect2 and combined_sample$strelka2
S = 3.3543e+10, p-value < 2.2e-16
alternative hypothesis: true rho is not equal to 0
sample estimates:
      rho 
0.7808425 
cor.test(combined_sample$mutect2, combined_sample$strelka2, method = "pearson")

    Pearson's product-moment correlation

data:  combined_sample$mutect2 and combined_sample$strelka2
t = 778.22, df = 9718, p-value < 2.2e-16
alternative hypothesis: true correlation is not equal to 0
95 percent confidence interval:
 0.9917519 0.9923801
sample estimates:
      cor 
0.9920722 

Plot Transition/Transversions

maftools::plotTiTv(maftools::titv(strelka2))

maftools::plotTiTv(maftools::titv(mutect2))

Set up new variables

Here we will make these new variables for both Mutect2 and Strelka2 dataset: - Calculate VAF for each - Make a mutation ID by concatenating gene name, allele, tumor ID, and start position - Summarize the biotype variable for whether or not it is a coding gene.

Let’s do this for Strelka2 first.

strelka2_vaf <- strelka2@data %>%
  dplyr::mutate(
    vaf = as.numeric(t_alt_count) / (as.numeric(t_ref_count) +
      as.numeric(t_alt_count)),
    base_change = paste0(Reference_Allele, ">", Allele),
    coding = dplyr::case_when(
      BIOTYPE != "protein_coding" ~ "non-coding",
      TRUE ~ "protein_coding"
    )
  ) %>%
  dplyr::mutate(change = dplyr::case_when(
    grepl("^-", base_change) ~ "insertion",
    grepl("-$", base_change) ~ "deletion",
    nchar(base_change) > 3 ~ "long_change",
    TRUE ~ base_change
  )) %>%
  dplyr::mutate(
    mutation_id = paste0(
      Hugo_Symbol, "_",
      change, "_",
      Start_Position, "_",
      Tumor_Sample_Barcode
    ),
    general_id = paste0(Hugo_Symbol, "_", Tumor_Sample_Barcode)
  ) %>%
  dplyr::select(-which(apply(is.na(.), 2, all)))
NAs introduced by coercion
# Take a look at this df
strelka2_vaf

Now we will do the same for MuTect2.

mutect2_vaf <- mutect2@data %>%
  dplyr::mutate(
    vaf = as.numeric(t_alt_count) / (as.numeric(t_ref_count) +
      as.numeric(t_alt_count)),
    base_change = paste0(Reference_Allele, ">", Allele),
    coding = dplyr::case_when(
      BIOTYPE != "protein_coding" ~ "non-coding",
      TRUE ~ "protein_coding"
    )
  ) %>%
  dplyr::mutate(change = dplyr::case_when(
    grepl("^-", base_change) ~ "insertion",
    grepl("-$", base_change) ~ "deletion",
    nchar(base_change) > 3 ~ "long_change",
    TRUE ~ base_change
  )) %>%
  dplyr::mutate(
    mutation_id = paste0(
      Hugo_Symbol, "_",
      change, "_",
      Start_Position, "_",
      Tumor_Sample_Barcode
    ),
    general_id = paste0(Hugo_Symbol, "_", Tumor_Sample_Barcode)
  ) %>%
  dplyr::select(-which(apply(is.na(.), 2, all)))

# Take a look at this df
mutect2_vaf

Combine MuTect2 and Strelka2 data.frames into one data.frame

Save to a TSV file.

# Merge these data.frames together
vaf_df <- strelka2_vaf %>%
  dplyr::full_join(mutect2_vaf,
    by = "mutation_id",
    suffix = c(".strelka2", ".mutect2")
  ) %>%
  # Make a variable that denotes which dataset it is in.
  dplyr::mutate(dataset = dplyr::case_when(
    is.na(Allele.mutect2) ~ "strelka2_only",
    is.na(Allele.strelka2) ~ "mutect2_only",
    TRUE ~ "both"
  )) %>%
  readr::write_tsv(file.path("results", "combined_results.tsv"))

Session Info:

sessionInfo()
R version 3.6.1 (2019-07-05)
Platform: x86_64-apple-darwin15.6.0 (64-bit)
Running under: macOS Mojave 10.14.5

Matrix products: default
BLAS:   /System/Library/Frameworks/Accelerate.framework/Versions/A/Frameworks/vecLib.framework/Versions/A/libBLAS.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRlapack.dylib

locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8

attached base packages:
[1] parallel  stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] Biobase_2.44.0      BiocGenerics_0.30.0

loaded via a namespace (and not attached):
 [1] pkgload_1.0.2        tidyr_0.8.3          splines_3.6.1        jsonlite_1.6        
 [5] foreach_1.4.7        assertthat_0.2.1     yaml_2.2.0           remotes_2.1.0       
 [9] sessioninfo_1.1.1    lattice_0.20-38      pillar_1.4.2         backports_1.1.4     
[13] glue_1.3.1           digest_0.6.20        RColorBrewer_1.1-2   colorspace_1.4-1    
[17] Matrix_1.2-17        htmltools_0.3.6      plyr_1.8.4           pkgconfig_2.0.2     
[21] devtools_2.1.0       bibtex_0.4.2         purrr_0.3.2          xtable_1.8-4        
[25] scales_1.0.0         processx_3.4.1       VennDiagram_1.6.20   tibble_2.1.3        
[29] pkgmaker_0.27        styler_1.1.1.9003    ggplot2_3.2.1        usethis_1.5.1       
[33] withr_2.1.2          lazyeval_0.2.2       cli_1.1.0            survival_2.44-1.1   
[37] magrittr_1.5         crayon_1.3.4         memoise_1.1.0        evaluate_0.14       
[41] ps_1.3.0             fs_1.3.1             doParallel_1.0.15    NMF_0.21.0          
[45] pkgbuild_1.0.4       tools_3.6.1          registry_0.5-1       data.table_1.12.2   
[49] prettyunits_1.0.2    hms_0.5.0            formatR_1.7          gridBase_0.4-7      
[53] stringr_1.4.0        munsell_0.5.0        cluster_2.1.0        rngtools_1.4        
[57] lambda.r_1.2.3       maftools_2.0.15      callr_3.3.1          compiler_3.6.1      
[61] rlang_0.4.0          futile.logger_1.4.3  grid_3.6.1           iterators_1.0.12    
[65] rstudioapi_0.10      colorblindr_0.1.0    base64enc_0.1-3      rmarkdown_1.14      
[69] testthat_2.2.1       gtable_0.3.0         codetools_0.2-16     curl_4.0            
[73] rematch2_2.1.0       reshape2_1.4.3       R6_2.4.0             knitr_1.24          
[77] dplyr_0.8.3          zeallot_0.1.0        rprojroot_1.3-2      futile.options_1.0.1
[81] readr_1.3.1          desc_1.2.0           stringi_1.4.3        Rcpp_1.0.2          
[85] vctrs_0.2.0          wordcloud_2.6        tidyselect_0.2.5     xfun_0.8            
---
title: "Set up combined data of Mutect2 and Strelka2"
output:   
  html_notebook: 
    toc: true
    toc_float: true
---

Candace Savonen - CCDL for ALSF

This notebook sets up the MAF data files for comparison and does some first 
line analyses.

It is the first notebook in this series which addresses [issue \# 30 in OpenPBTA](https://github.com/AlexsLemonade/OpenPBTA-analysis/issues/30).

## Usage

To run this from the command line, use:
```
Rscript -e "rmarkdown::render('analyses/mutect2-vs-strelka2/01-set-up.Rmd', 
                              clean = TRUE)"
```

 _This assumes you are in the top directory of the repository._

## Set Up

```{r}
# We need maftools - this will be added to the running Docker issue whenever it is up
if (!("maftools" %in% installed.packages())) {
  devtools::install_github("PoisonAlien/maftools")
}
```

Get `magrittr` pipe

```{r}
`%>%` <- dplyr::`%>%`
```

### Directories and files

Path to the symlinked data obtained via `bash download-data.sh`.

```{r}
data_dir <- file.path("..", "..", "data")
scratch_dir <- file.path("..", "..", "scratch")
```

Create output directories in this analysis folder.

```{r}
if (!dir.exists("results")) {
  dir.create("results")
}
if (!dir.exists("plots")) {
  dir.create("plots")
}
```

## Read in the metadata information

Running `maftools::read.maf` takes a lot of computing power and time, so to 
avoid having to run this for both datasets everytime we want to re-run this 
notebook or the analyses in the other notebook, I've set this up to save the 
`MAF` objects as `RDS` files.

First let's establish the file paths.

```{r}
# File paths for the needed files for this analysis
  metadata_dir <- file.path(scratch_dir, "metadata_filtered_maf_samples.tsv")
strelka2_dir <- file.path(scratch_dir, "strelka2.RDS")
mutect2_dir <- file.path(scratch_dir, "mutect2.RDS")
```

## Read in the Strelka2 and Mutect2 data

Will read in as an `maftools` object from an RDS file, unless `maftools` has not
been run on them yet.
Establish whether the files we need for this already exist before running it 
again. 

If you trying to run the set up step in a Docker container, it will likely be 
out of memory killed, unless you have ~50GB you can allot to Docker. 

Prep the metadata to be used as the `clinicalData` for maftools it it hasn't been 
prepped yet. 

```{r}
# Get a vector of whether these exist
files_needed <- file.exists(metadata_dir, strelka2_dir, mutect2_dir)

if (all(files_needed)) {
  # Read the ready-to-go files if these files exist
  metadata <- metadata <- readr::read_tsv(metadata_dir)
  strelka2 <- readRDS(strelka2_dir)
  mutect2 <- readRDS(mutect2_dir)
} else { # If any of the needed files don't exist, rerun this process:
  # Only import the sample names
  strelka2_samples <- data.table::fread(file.path(
    data_dir,
    "pbta-snv-strelka2.vep.maf.gz"
  ),
  select = "Tumor_Sample_Barcode",
  skip = 1,
  data.table = FALSE
  )

  mutect2_samples <- data.table::fread(file.path(
    data_dir,
    "pbta-snv-mutect2.vep.maf.gz"
  ),
  select = "Tumor_Sample_Barcode",
  skip = 1,
  data.table = FALSE
  )

  # Isolate metadata to only the samples that are in the datasets
  metadata <- readr::read_tsv(data_dir, "pbta-histologies.tsv") %>%
    dplyr::filter(Kids_First_Biospecimen_ID %in% c(strelka2_samples, mutect2_samples)) %>%
    dplyr::distinct(Kids_First_Biospecimen_ID, .keep_all = TRUE) %>%
    dplyr::arrange() %>%
    readr::write_tsv(file.path(scratch_dir, "metadata_filtered_maf_samples.tsv"))

  # Read in original strelka file with maftools
  strelka <- maftools::read.maf(file.path(data_dir, "pbta-snv-strelka2.vep.maf.gz"),
    clinicalData = metadata
  )

  # Save to RDS so we don't have to run this again
  saveRDS(strelka, strelka2_dir)

  # Same for MuTect2
  mutect2 <- maftools::read.maf(file.path(data_dir, "pbta-snv-mutect2.vep.maf.gz"),
    clinicalData = metadata
  )
  saveRDS(mutect2, mutect2_dir)
}
```

## Get summaries and write them to TSVs 

Get gene summaries and write to TSV files. 

```{r}
strelka2_gene_sum <- maftools::getGeneSummary(strelka2) %>%
  readr::write_tsv(file.path(
    "results",
    "strelka2_gene_summary.tsv"
  ))

mutect2_gene_sum <- maftools::getGeneSummary(mutect2) %>%
  readr::write_tsv(file.path(
    "results",
    "mutect2_gene_summary.tsv"
  ))
```

Get sample summaries and write to TSV files. 

```{r}
strelka2_sample_sum <- maftools::getSampleSummary(strelka2) %>%
  readr::write_tsv(file.path(
    "results",
    "strelka2_sample_summary.tsv"
  ))

mutect2_sample_sum <- maftools::getSampleSummary(mutect2) %>%
  readr::write_tsv(file.path(
    "results",
    "mutect2_sample_summary.tsv"
  ))
```

## Number of mutations per gene correlation 

```{r}
combined_gene <- mutect2_gene_sum %>%
  dplyr::full_join(strelka2_gene_sum, by = "Hugo_Symbol") %>%
  reshape2::melt(id = "Hugo_Symbol") %>%
  dplyr::mutate(dataset = as.character(grepl(".x$", variable))) %>%
  dplyr::mutate(dataset = dplyr::recode(dataset,
    `TRUE` = "mutect2",
    `FALSE` = "strelka2"
  )) %>%
  dplyr::mutate(variable = gsub(".x$|.y$", "", variable)) %>%
  tidyr::spread("dataset", "value")
```

Let's get a correlation test on the genes overall.

```{r}
cor.test(combined_gene$mutect2, combined_gene$strelka2, method = "spearman")
cor.test(combined_gene$mutect2, combined_gene$strelka2, method = "pearson")
```

## Number of mutations per sample correlation. 

```{r}
combined_sample <- mutect2_sample_sum %>%
  dplyr::full_join(strelka2_sample_sum, by = "Tumor_Sample_Barcode") %>%
  reshape2::melt(id = "Tumor_Sample_Barcode") %>%
  dplyr::mutate(dataset = as.character(grepl(".x$", variable))) %>%
  dplyr::mutate(dataset = dplyr::recode(dataset,
    `TRUE` = "mutect2",
    `FALSE` = "strelka2"
  )) %>%
  dplyr::mutate(variable = gsub(".x$|.y$", "", variable)) %>%
  tidyr::spread("dataset", "value")
```

Let's get a correlation test on the genes overall.

```{r}
cor.test(combined_sample$mutect2, combined_sample$strelka2, method = "spearman")
cor.test(combined_sample$mutect2, combined_sample$strelka2, method = "pearson")
```

## Plot Transition/Transversions

```{r}
maftools::plotTiTv(maftools::titv(strelka2))
```

```{r}
maftools::plotTiTv(maftools::titv(mutect2))
```

## Set up new variables

Here we will make these new variables for both Mutect2 and Strelka2 dataset:
- Calculate VAF for each
- Make a mutation ID by concatenating gene name, allele, tumor ID, and start position
- Summarize the biotype variable for whether or not it is a coding gene. 

Let's do this for Strelka2 first. 

```{r}
strelka2_vaf <- strelka2@data %>%
  dplyr::mutate(
    vaf = as.numeric(t_alt_count) / (as.numeric(t_ref_count) +
      as.numeric(t_alt_count)),
    base_change = paste0(Reference_Allele, ">", Allele),
    coding = dplyr::case_when(
      BIOTYPE != "protein_coding" ~ "non-coding",
      TRUE ~ "protein_coding"
    )
  ) %>%
  dplyr::mutate(change = dplyr::case_when(
    grepl("^-", base_change) ~ "insertion",
    grepl("-$", base_change) ~ "deletion",
    nchar(base_change) > 3 ~ "long_change",
    TRUE ~ base_change
  )) %>%
  dplyr::mutate(
    mutation_id = paste0(
      Hugo_Symbol, "_",
      change, "_",
      Start_Position, "_",
      Tumor_Sample_Barcode
    ),
    general_id = paste0(Hugo_Symbol, "_", Tumor_Sample_Barcode)
  ) %>%
  dplyr::select(-which(apply(is.na(.), 2, all)))

# Take a look at this df
strelka2_vaf
```

Now we will do the same for MuTect2.

```{r}
mutect2_vaf <- mutect2@data %>%
  dplyr::mutate(
    vaf = as.numeric(t_alt_count) / (as.numeric(t_ref_count) +
      as.numeric(t_alt_count)),
    base_change = paste0(Reference_Allele, ">", Allele),
    coding = dplyr::case_when(
      BIOTYPE != "protein_coding" ~ "non-coding",
      TRUE ~ "protein_coding"
    )
  ) %>%
  dplyr::mutate(change = dplyr::case_when(
    grepl("^-", base_change) ~ "insertion",
    grepl("-$", base_change) ~ "deletion",
    nchar(base_change) > 3 ~ "long_change",
    TRUE ~ base_change
  )) %>%
  dplyr::mutate(
    mutation_id = paste0(
      Hugo_Symbol, "_",
      change, "_",
      Start_Position, "_",
      Tumor_Sample_Barcode
    ),
    general_id = paste0(Hugo_Symbol, "_", Tumor_Sample_Barcode)
  ) %>%
  dplyr::select(-which(apply(is.na(.), 2, all)))

# Take a look at this df
mutect2_vaf
```

## Combine MuTect2 and Strelka2 data.frames into one data.frame

Save to a TSV file.

```{r}
# Merge these data.frames together
vaf_df <- strelka2_vaf %>%
  dplyr::full_join(mutect2_vaf,
    by = "mutation_id",
    suffix = c(".strelka2", ".mutect2")
  ) %>%
  # Make a variable that denotes which dataset it is in.
  dplyr::mutate(dataset = dplyr::case_when(
    is.na(Allele.mutect2) ~ "strelka2_only",
    is.na(Allele.strelka2) ~ "mutect2_only",
    TRUE ~ "both"
  )) %>%
  readr::write_tsv(file.path("results", "combined_results.tsv"))
```

Session Info: 

```{r}
sessionInfo()
```
